| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
HIF-2α Translation Inhibitor targets the translation of hypoxia-inducible factor-2α (HIF-2α) mRNA. It suppresses HIF-2α translation by enhancing the binding of IRP1 (Iron-Regulatory Protein 1) to the IRE (Iron-Responsive Element) region at the 5' UTR of the HIF-2α message. This mechanism links the 5'UTR iron-responsive element to oxygen sensing. The compound decreases both constitutive and hypoxia-induced HIF-2α protein expression independent of HIF-2α mRNA expression, HIF-2α protein stability, or mTOR activity.
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| ln Vitro |
In a mTOR-independent way, HIF-2α-IN-4 (Compound 76) (10 μM; 786-O cells) decreases the translation of HIF-2α mRNA [1]. In both normal and hypoxic oxygen circumstances, HIF-2α-IN-4 decreases the expression of HIF-2α target genes and HIF-2α protein [1].
In vitro, HIF-2α Translation Inhibitor potently inhibits HIF-2α translation with an IC50 of 5 μM. It inhibits constitutive gene expression in a hypoxia-response element (HRE) reporter assay using VHL-deficient 786-O renal cell carcinoma (RCC) cells (IC50 = 5 μM). The compound decreases both constitutive and hypoxia-induced HIF-2α protein expression. It is cell-permeable and links the 5'UTR iron-responsive element to oxygen sensing. |
| ln Vivo |
Specific in vivo data for HIF-2α Translation Inhibitor are limited. Given its potent in vitro activity and ability to inhibit HIF-2α translation, the compound has potential for in vivo studies in models of renal cell carcinoma and other cancers where HIF-2α is a key driver. However, specific published in vivo protocols for this compound are not detailed. The compound is for research use only.
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| Enzyme Assay |
The HIF-2α translation inhibitory activity is assessed using cell-based reporter assays. VHL-deficient 786-O renal cell carcinoma (RCC) cells containing a hypoxia-response element (HRE) reporter are treated with the compound at various concentrations. Reporter activity is measured, and IC50 values are calculated. HIF-2α protein levels are measured by Western blot. HIF-2α mRNA levels are measured by qPCR to confirm the translational mechanism.
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| Cell Assay |
For cellular studies, VHL-deficient 786-O RCC cells and other cancer cell lines are cultured in appropriate media. Cells are treated with HIF-2α Translation Inhibitor at various concentrations (e.g., 0.1-50 μM) for 24-72 hours. HIF-2α protein levels are measured by Western blot using anti-HIF-2α antibodies. HIF-2α target gene expression (e.g., VEGF, EPO) is measured by qPCR. Cell viability is assessed using MTT or similar assays. The compound is typically dissolved in DMSO and diluted in culture media. The compound has a molecular weight of 287.31 g/mol and a molecular formula of C₉H₉N₃O₄S₂.
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| Animal Protocol |
In vivo studies for HIF-2α Translation Inhibitor would be conducted in appropriate animal models. For renal cell carcinoma research, xenograft models using 786-O cells would be employed. The compound would be administered via oral gavage or intraperitoneal injection. Tumor volumes would be measured, and HIF-2α protein levels and target gene expression in tumors would be assessed. However, specific published protocols for this compound are not available.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for HIF-2α Translation Inhibitor are not extensively reported. The compound has a molecular weight of 287.31 g/mol and a molecular formula of C₉H₉N₃O₄S₂. It is soluble in DMSO for in vitro studies. Pharmacokinetic studies would be required to determine parameters such as half-life, Cmax, oral bioavailability, and tissue distribution in animal models. The compound should be stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Specific toxicological data for HIF-2α Translation Inhibitor are not reported. As a research compound, comprehensive toxicology studies including acute, subchronic, and genotoxicity assessments have not been reported. The compound is for research use only. Standard safety precautions should be taken when handling, and the compound should be used in a controlled laboratory environment.
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| References | |
| Additional Infomation |
HIF-2α Translation Inhibitor (HIF-2α-IN-4) is a potent HIF-2α translation inhibitor with an IC50 of 5 μM. It suppresses HIF-2α translation by enhancing IRP1 binding to the IRE at the 5' UTR. It decreases both constitutive and hypoxia-induced HIF-2α protein expression. No clinical trials exist. For research use only.
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| Molecular Formula |
C9H9N3O4S2
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|---|---|
| Molecular Weight |
287.315459012985
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| Exact Mass |
287.003
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| CAS # |
882268-69-1
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| PubChem CID |
2820256
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
18
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| Complexity |
500
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N#CC(S(C)(=O)=O)=NNC1=C(C(OC)=O)SC=C1
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| InChi Key |
OOGAPDPPVHJYGJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H9N3O4S2/c1-16-9(13)8-6(3-4-17-8)11-12-7(5-10)18(2,14)15/h3-4,11H,1-2H3
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| Chemical Name |
methyl 3-[2-[cyano(methylsulfonyl)methylidene]hydrazinyl]thiophene-2-carboxylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~174.02 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.70 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4804 mL | 17.4022 mL | 34.8044 mL | |
| 5 mM | 0.6961 mL | 3.4804 mL | 6.9609 mL | |
| 10 mM | 0.3480 mL | 1.7402 mL | 3.4804 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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